In 1990, the H3N2 influenza a strain was changed from A/Shanghai/1-1/87 to A/Shanghai/16/89 in accordance with the recommendations of the World Health Organization as a consequence of changes in circulating human influenza virus strains in the United States and elsewhere. During the decision making process, several new strains, including A/Guangdong/39/89, were in contention. Consequently, single-radial-immunodiffusion (SRID) potency testing antisera to both A/Shanghai/16/89 and A/Guangdong/39/89 were produced by immunizing sheep with bromelain purified hemagglutinin produced by Connaught Laboratories, Inc. for use by the Center for Biologics Evaluation and Research. These two viruses are virtually indistinguishable in hemagglutination-inhibition tests. Experience with SRID testing has demonstrated that antisera made to very closely related strains can yield somewhat different potency values even when homologous reference antigens are used. We are in the process of comparing these two antisera in SRID assays with homologous and heterologous antigens to determine the percent difference, if any, in potency values. This information should prove useful in future years in assessing the importance of obtaining homologous antiserum (a costly and time consuming process) or using closely related or indistinguishable heterologous antisera which may be already available. Connaught also produced detergent disrupted, purified hemagglutinin for the Center's use in standardizing a lyophilized potency reference antigen. As in the past, this reference was standardized in collaboration with the World Health Organization and their reference antigen. Although the process of standardizing reference antigens has improved through the years since the inception of SRID testing in 1978, we will continue to search for tools which will help in reducing the time involved while increasing our understanding of the mechanism of immunodiffusion and the relationship of different antigens and antisera.